Gene Knockout and Transgenic Technologies in Risk Assessment: The Next Generation

Molecular Carcinogenesis

Volumn 20, Issue 3, 1997, Pages 262-274

  Rosenberg, Michael P ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

Carcinogenesis; ES cells; Risk assessment; Transgenic mice

Indexed keywords

MUS MUSCULUS; RODENTIA;

ANIMAL; CARCINOGEN TESTING; DISEASE MODEL; EXPERIMENTAL NEOPLASM; GENETIC PROCEDURES; GENETICS; MOUSE; MOUSE MUTANT; REVIEW; RISK ASSESSMENT; TRANSGENE; TRANSGENIC MOUSE;

ANIMALS; CARCINOGENICITY TESTS; DISEASE MODELS, ANIMAL; GENETIC TECHNIQUES; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; NEOPLASMS, EXPERIMENTAL; RISK ASSESSMENT; TRANSGENES;

EID: 0031280252     PISSN: 08991987     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1098-2744(199711)20:3<262::AID-MC2>3.0.CO;2-N     Document Type: Review

References (179)

1. Provost GS, Kretz PL, Hamner RT, et al. Transgenic systems for in vivo mutation analysis. Mutat Res 288:133-149, 1993.
2. Ashby J, Tinwell H. Use of transgenic mouse lacI/Z mutation assays in genetic toxicology. Mutagenesis 9:179-181, 1994.
3. Mirsalis JC, Monforte JA, Winegar RA. Transgenic animal models for measuring mutations in vivo. Crit Rev Toxicol 24:255-280, 1994.
4. Morrison V, Ashby J. A preliminary evaluation of the performance of the Muta Mouse (lacZ) and Big Blue (lacI) transgenic mouse mutation assays. Mutagenesis 9:367-376, 1994.
5. Shephard SE, Lutz WK, Schlatter C. The lacI transgenic mouse mutagenicity assay: Quantitative evaluation in comparison to tests for carcinogenicity and cytogenetic damage in vivo. Mutat Res 306:119-128, 1994.
6. Douglas GR, Jiao J, Gingerich JD, Gossen JA, Soper LM. Temporal and molecular characteristics of mutations induced by ethylnitrosourea in germ cells isolated from seminiferous tubules and in spermatozoa of lacZ transgenic mice. Proc Natl Acad Sci USA 92:7485-7489, 1995.
7. Nishino H, Knöll A, Buettner VL, et al. p53 wild-type and p53 nullizygous Big Blue transgenic mice have similar frequencies and patterns of observed mutation in liver, spleen and brain. Oncogene 11:263-270, 1995.
8. Tinwell H, Liegibel U, Krebs O, Schmezer P, Favor J, Ashby J. Comparison of lacI and lacZ transgenic mouse mutation as-says: An EU-sponsored interlaboratory study. Mutat Res 335:185-190, 1995.
9. Tennant RW, Spalding J, French JE. Evaluation of transgenic mouse bioassays for identifying carcinogens and noncarcinogens. Mutat Res 365:119-127, 1996.
10. Gossen M, Bujard H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci USA 89:5547-5551, 1992.
11. Furth PA, St. Onge L, Böger H, et al. Temporal control of gene expression in transgenic mice by a tetracycline-responsive promoter. Proc Natl Acad Sci USA 91:9302-9306, 1994.
12. Gossen M, Bonin AL, Freundlieb S, Bujard H. Inducible gene expression systems for higher eukaryotic cells. Curr Opin Biotechnol 5:516-520, 1994.
13. Kistner A, Gossen M, Zimmermann F, et al. Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. Proc Natl Acad Sci USA 93:10933-10938, 1996.
14. Gossen M, Bujard H. Anhydrotetracycline, a novel effector for tetracycline controlled gene expression systems in eukaryotic cells. Nucleic Acids Res 21:4411-4412, 1993.
15. Chrast-Balz J, Van Huijsduijnen RH. Bi-directional gene switching with the tetracycline repressor and a novel tetracycline antagonist. Nucleic Acids Res 24:2900-2904, 1996.
16. Kucera GT, Bortner DZ, Rosenberg MP. Overexpression of an Agouti cDNA in the skin of transgenic mice recapitulates dominant coat color phenotypes of spontaneous mutants. Dev Biol 173:162-173, 1996.
17. Gossen M, Freundlieb S, Bender G, Muller G, Hillen W, Bujard H. Transcriptional activation by tetracyclines in mammalian cells. Science 268:1766-1769, 1995.
18. Ewald D, Li MG, Efrat S, et al. Time-sensitive reversal of hyperplasia in transgenic mice expressing SV40 T antigen. Science 273:1384-1386, 1996.
19. Fiering S, Kim CG, Epner EM, Groudine M. An "in-out" strategy using gene targeting and FLP recombinase for the functional dissection of complex DNA regulatory elements: Analysis of the β-globin locus control region. Proc Natl Acad Sci USA 90:8469-8473, 1993.
20. Pan G, Luetke K, Sadowski PD. Mechanism of cleavage and ligation by FLP recombinase: Classification of mutations in FLP protein by in vitro complementation analysis. Mol Cell Biol 13:3167-3175, 1993.
21. Fukushige S, Sauer B. Genomic targeting with a positive-selection lox integration vector allows highly reproducible gene expression in mammalian cells. Proc Natl Acad Sci USA 89:7905-7909, 1992.
22. Sauer B. Identification of cryptic lox sites in the yeast genome by selection for cre-mediated chromosome translocations that confer multiple drug resistance. J Mol Biol 223: 911-928, 1992.
23. Baubonis W, Sauer B. Genomic targeting with purified Cre recombinase. Nucleic Acids Res 21:2025-2029, 1993.
24. Sauer B. Manipulation of transgenes by site-specific recombination: Use of Cre recombinase. Methods Enzymol 225:890-900, 1993.
25. Araki K, Araki M, Miyazaki J, Vassalli P. Site-specific recombination of a transgene in fertilized eggs by transient expression of Cre recombinase. Proc Natl Acad Sci USA 92: 160-164, 1995.
26. St. Onge L, Furth PA, Gruss P. Temporal control of the Cre recombinase in transgenic mice by a tetracycline responsive promoter. Nucleic Acids Res 24:3875-3877, 1996.
27. Albert H, Dale EC, Lee E, Ow W. Site-specific integration of DNA into wild-type and mutant lox sites placed in the plant genome. Plant J 714:649-659, 1995.
28. Bronson SK, Plaehn EG, Kluckman KD, Hagaman JR, Maeda N, Smithies O. Single-copy transgenic mice with chosen-site integration. Proc Natl Acad Sci USA 93:9067-9072, 1996.
29. Bradley A, Liu P. Target practice in transgenics. Nat Genet 14:121-123, 1996.
30. Smith AJH, De Sousa MA, Kwabi-Addo B, Heppell-Parton A, Impey H, Rabbitts P. A site-directed chromosomal translocation induced in embryonic stem cells by Cre-loxP recombination. Nat Genet 9:376-385, 1995.
31. Metzger D, Clifford J, Chiba H, Chambon P. Conditional site-specific recombination in mammalian cells using a ligand-dependent chimeric Cre recombinase. Proc Natl Acad Sci USA 92:6991-6995, 1995.
32. Feil R, Brocard J, Mascrez B, LeMeur M, Metzger D, Chambon P. Ligand-activated site-specific recombination in mice. Proc Natl Acad Sci USA 93:10887-10890, 1996.
33. Wang Y, Krushel LA, Edelman GM. Targeted DNA recombination in vivo using an adenovirus carrying the cre recombinase gene. Proc Natl Acad Sci USA 93:3932-3936, 1996.
34. Vogelstein B, Kinzler KW. The multistep nature of cancer. Trends Genet 9:138-141, 1993.
35. Cho KR, Fearon ER. DCC: Linking tumor suppressor genes and altered cell surface interactions in cancer. Curr Opin Genet Dev 5:72-78, 1995.
36. Morin PJ, Vogelstein B, Kinzler KW. Apoptosis and APC in colorectal tumorigenesis. Proc Natl Acad Sci USA 93:7950-7954, 1996.
37. Hermiston ML, Gordon JI. Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin. Science 270:1203-1207, 1995.
38. Luongo C, Gould KA, Su L-K, et al. Mapping of multiple intestinal neoplasia (Min) to proximal chromosome 18 of the mouse. Genomics 15:3-8, 1993.
39. Min: A mouse model for intestinal and mammary tumorigenesis. Eur J Cancer [A] 31:1061-1064, 1995.
40. Wong MH, Hermiston ML, Syder AJ, Gordon JI. Forced expression of the tumor suppressor adenomatosis polyposis coli protein induces disordered cell migration in the intestinal epithelium. Proc Natl Acad Sci USA 93:9588-9593, 1996.
41. Dietrich WF, Lander ES, Smith JS, et al. Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse. Cell 75:631-639, 1993.
42. Min-induced intestinal neoplasia. Cell 81:957-966, 1995.
43. Dinchuk JE, Car BD, Focht RJ, et al. Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II. Nature 378:406-409, 1995.
44. Langenbach R, Morham SG, Tiano HF, et al. Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration. Cell 83:483-492, 1995.
45. Morham SG, Langenbach R, Loftin CD, et al. Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse. Cell 83:473-482, 1995.
46. Oshima M, Dinchuk JE, Kargman SL, et al. Suppression of intestinal polyposis in ApcDelta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 87:803-809, 1996.
47. Berx G, Cleton-Jansen AM, Nollet F, et al. E-cadherin is a tumour invasion suppressor gene mutated in human lobular breast cancers. EMBO J 14:6107-6115, 1995.
48. Berx G, Cleton-Jansen AM, Strumane K, et al. E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain. Oncogene 13:1919-1925, 1996.
49. D'souza B, Taylor-Papadimitriou J. Overexpression of ERBB2 in human mammary epithelial cells signals inhibition of transcription of the E-cadherin gene. Proc Natl Acad Sci USA 91:7202-7206, 1994.
50. Larue L, Ohsugi M, Hirchenhain J, Kemler R. E-cadherin null mutant embryos fail to form a trophectoderm epithelium. Proc Natl Acad Sci USA 91:8263-8267, 1994.
51. Riethmacher, D, Brinkmann V, Birchmeier C. A targeted mutation in the mouse E-cadherin gene results in defective preimplantation development. Proc Natl Acad Sci USA 92:855-859, 1995.
52. Hülsken J, Birchmeier W, Behrens J. E-cadherin and APC compete for the interaction with β-catenin and the cytoskeleton. J Cell Biol 127:2061-2069, 1994.
53. Su L-K, Vogelstein B, Kinzler KW. Association of the APC tumor suppressor protein with catenins. Science 262:1734-1737, 1993.
54. Brannan CI, Perkins AS, Vogel KS, et al. Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues. Genes Dev 8:1019-1029, 1994.
55. Jacks T, Shih T, Schmitt E, Bronson R, Bernards A, Weinberg R. Tumour predisposition in mice heterozygous for a targeted mutation in Nf1. Nat Genet 7:353-361, 1994.
56. Albano RM, Arkell R, Beddington RSP, Smith JC. Expression of inhibin subunits and follistatin during postimplantation mouse development: Decidual expression of activin and expression of follistatin in primitive streak, somites and hindbrain. Development 120:803-813, 1994.
57. Feijen A, Goumans MJ, Van den Eijnden-van Raaij AJM. Expression of activin subunits, activin receptors and follistatin in postimplantation mouse embryos suggests specific developmental functions for different activins. Development 120:3621-3637, 1994.
58. Matzuk MM, Finegold MJ, Mathér JP, Krummen L, Lu H, Bradley A. Development of cancer cachexia-like syndrome and adrenal tumors in inhibin-deficient mice. Proc Natl Acad Sci USA 91:8817-8821, 1994.
59. Shikone T, Matzuk MM, Perlas E, et al. Characterization of gonadal sex cord-stromal tumor cell lines from inhibin-α and p53-deficient mice: The role of activin as an autocrine growth factor. Mol Endocrinol 8:983-995, 1994.
60. Vassalli A, Matzuk MM, Gardner HAR, Lee K-F, Jaenisch R. Activin/inhibin βB subunit gene disruption leads to defects in eyelid development and female reproduction. Genes Dev 8:414-427, 1994.
61. Matzuk MM, Kumar TR, Bradley A. Different phenotypes for mice deficient in either activins or activin receptor type II. Nature 374:356-360, 1995.
62. Coerver KA, Woodruff TK, Finegold MJ, Mather J, Bradley A, Matzuk MM. Activin signaling through activin receptor type II causes the cachexia-like symptoms in inhibin-deficient mice. Mol Endocrinol 10:534-543, 1996.
63. Johnson DW, Berg JN, Baldwin MA, et al. Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nat Genet 13:189-195, 1996.
64. Li E, Beard C, Forster AC, Bestor TH, Jaenisch R. DNA methylation, genomic imprinting, and mammalian development. Cold Spring Harbor Symp Quant Biol 58:297-305, 1993.
65. Li E, Beard C, Jaenisch R. Role for DNA methylation in genomic imprinting. Nature 366:362-365, 1993.
66. Sapienza C. Genome imprinting and dominance modification. Ann NY Acad Sci 564:24-38, 1989.
67. Reik W. Cancer genetics: Imprinting in leukaemia. Nature 359:362-363, 1992.
68. Sapienza C. Genome imprinting and cancer genetics. Semin Cancer Biol 3:151-158, 1992.
69. Peterson K, Sapienza C. Imprinting the genome: Imprinted genes, imprinting genes, and a hypothesis for their interaction. Annu Rev Genet 27:7-31, 1993.
70. Gonzalez-Zulueta M, Bender CM, Yang AS, et al. Methylation of the 5′ CpG island of the p16/CDKN2 tumor suppressor gene in normal and transformed human tissues correlates with gene silencing. Cancer Res 55:4531-4535, 1995.
71. Herman JG, Merlo A, Mao L, et al. Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res 55:4525-4530, 1995.
72. INK4 protein induction by 5-aza 2′deoxycytidine. Oncogene 11:1211-1216, 1995.
73. Fueyo J, Gomez-Manzano C, Bruner JM, et al. Hypermethylation of the CpG island of p16/CDKN2 correlates with gene inactivation in gliomas. Oncogene 13:1615-1619, 1996.
74. Costello JF, Berger MS, Huang HJS, Cavenee WK. Silencing of p16/CDKN2 expression in human gliomas by methylation and chromatin condensation. Cancer Res 56:2405-2410, 1996.
75. INK4, the product of the putative tumor suppressor gene MTS1. Oncogene 9:3475-3482, 1994.
76. Lukas J, Parry D, Aagaard L, et al. Retinoblastoma-protein-dependent cell-cycle inhibition by the tumour suppressor p16. Nature 375:503-506, 1995.
77. ink4 requires functional retinoblastoma protein. Proc Natl Acad Sci USA 92:6289-6293, 1995.
78. INK4/MTS1 tumour suppressor gene product. EMBO J 14:503-511, 1995.
79. CDKN2/INK4A. Curr Biol 6:84-91, 1996.
80. Zhan SL, Shapiro DN, Helman U. Loss of imprinting of IGF2 in Ewing's sarcoma. Oncogene 11:2503-2507, 1995.
81. Issa JPJ, Vertino PM, Boehm CD, Newsham IF, Baylin SB. Switch from monoallelic to biallelic human IGF2 promoter methylation during aging and carcinogenesis. Proc Natl Acad Sci USA 93:11757-11762, 1996.
82. Takeda S, Kondo M, Kumada T, et al. Allelic-expression imbalance of the insulin-like growth factor 2 gene in hepatocellular carcinomas and underlying disease. Oncogene 12:1589-1592, 1996.
83. Hao Y, Crenshaw T, Moulton T, Newcomb E, Tycko B. Tumour-suppressor activity of H79 RNA. Nature 365:764-767, 1993.
84. Banerjee S, Smallwood A. A chromatin model of IGF2/H19 imprinting. Nat Genet 11:237-238, 1995.
85. Li E, Bestor TH, Jaenisch R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915-926, 1992.
86. Tucker KL, Talbot D, Lee MA, Leonhardt H, Jaenisch R. Complementation of methylation deficiency in embryonic stem cells by a DNA methyltransferase minigene. Proc Natl Acad Sci USA 93:12920-12925, 1996.
87. Laird PW, Jaenisch R. DNA methylation and cancer. Hum Mol Genet 3:1487-1495, 1994.
88. Duan DR, Humphrey JS, Chen DYT, et al. Characterization of the VHL tumor suppressor gene product: Localization, complex formation, and the effect of natural inactivating mutations. Proc Natl Acad Sci USA 92:6459-6463, 1995.
89. Pal N, Wadey RB, Buckle B, Yeomans E, Pritchard J, Cowell JK. Preferential loss of maternal alleles in sporadic Wilms' tumour. Oncogene 5:1665-1668, 1990.
90. Little MH, Dunn R, Byrne JA, et al. Equivalent expression of paternally and maternally inherited WT1 alleles in normal fetal tissue and Wilms' tumours. Oncogene 7:635-641, 1992.
91. Rauscher III FJ. The WT1 Wilms tumor gene product: A developmentally regulated transcription factor in the kidney that functions as a tumor suppressor. FASEB J 7:896-903, 1993.
92. Herman JG, Latif F, Weng Y, et al. Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci USA 91:9700-9704, 1994.
93. Symonds H, Krall L, Remington L, et al. p53-dependent apoptosis suppresses tumor growth and progression in vivo. Cell 78:703-711, 1994.
94. Jiricny J. Colon cancer and DNA repair: Have mismatches met their match. Trends Genet 10:164-168, 1994.
95. De la Chapelle A, Peltomäki P. Genetics of hereditary colon cancer. Annu Rev Genet 29:329-348, 1995.
96. Dunlop MG. Mutator genes and mosaicism in colorectal cancer. Curr Opin Genet Dev 6:76-81, 1996.
97. Allemand I, Angulo JF. Transgenic and knock-out models for studying DNA repair. Biochimie 77:826-832, 1995.
98. Abbott C, Chambers D. Analysis of CAG trinucleotide repeats from mouse cDNA sequences. Ann Hum Genet 58:87-94, 1994.
99. Chambers DM, Abbott CM. Isolation and mapping of novel mouse brain DNA clones containing trinucleotide repeats, and demonstration of novel alleles in recombinant inbred strains. Genome Res 6:715-723, 1996.
100. Bingham PM, Scott MO, Wang S, et al. Stability of an expanded trinucleotide repeat in the androgen receptor gene in transgenic mice. Nat Genet 9:191-196, 1995.
101. Burright EN, Clark HB, Servadio A, et al. SCA1 transgenic mice: A model for neurodegeneration caused by an expanded CAG trinucleotide repeat. Cell 82:937-948, 1995.
102. Kooy RF, D'Hooge R, Reyniers E, et al. Transgenic mouse model for the fragile X syndrome. Am J Med Genet 64:241-245, 1996.
103. Mangiarini L, Sathasivam K, Seller M, et al. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87:493-506, 1996.
104. Roest HP, Van Klaveren J, De Wit J, et al. Inactivation of the HR6B ubiquitin-conjugating DNA repair enzyme in mice causes male sterility associated with chromatin modification. Cell 86:799-810, 1996.
105. Murti JR, Bumbulis M, Schimenti JC. High-frequency germ line gene conversion in transgenic mice. Mol Cell Biol 12:2545-2552, 1992.
106. Murti JR, Schimenti KJ, Schimenti JC. A recombination-based transgenic mouse system for genotoxicity testing. Mutat Res 307:583-595, 1994.
107. Hunter T, Pines J. Cyclins and cancer II: Cyclin D and CDK inhibitors come of age. Cell 79:573-582, 1994.
108. Sherr CJ. The ins and outs of RB: Coupling gene expression to the cell cycle clock. Trends Cell Biol 4:15-18, 1994.
109. Massagué J, Roberts JM. Cell multiplication - cell cycle 1995: Constructing cell physiology with molecular building blocks. Curr Opin Cell Biol 7:769-772, 1995.
110. Müller R. Transcriptional regulation during the mammalian cell cycle. Trends Genet 11:173-178, 1995.
111. Weinberg R. Prospects for cancer genetics. Cancer Surv 25:3-12, 1995.
112. Kip1 for restriction point control of the fibroblast cell cycle. Science 272:877-880, 1996.
113. Jacks T, Weinberg R. Cell-cycle control and its watchman. Nature 381:643-644, 1996.
114. Weinberg R. How cancer arises. Sci Am 275:62-70, 1996.
115. Xiong Y. Why are there so many CDK inhibitors? Biochim Biophys Acta 1288:1-5, 1996.
116. Hussussian CJ, Struewing JP, Goldstein AM, et al. Germline p16 mutations in familial melanoma. Nat Genet 8:15-21, 1994.
117. Cairns P, Polascik TJ, Eby Y, et al. Frequency of homozygous deletion at p16/CDKN2 in primary human tumours. Nat Genet 11:210-212, 1995.
118. Kodoru PRK, Zariwala M, Soni R, Gong JZ, Xiong Y, Broome JD. Deletion of cyclin-dependent kinase 4 inhibitor genes p15 and p16 in non-Hodgkin's lymphoma. Blood 86:2900-2905, 1995.
119. Bartkova J, Lukas J, Guldberg P, et al. The p16-cyclin D Cdk4-pRb pathway as a functional unit frequently altered in melanoma pathogenesis. Cancer Res 56:5475-5483, 1996.
120. INK4c in tumor-derived cell lines and primary tumors. Oncoqene 12:451-455, 1996.
121. INK4d, in tumor-derived cell lines and primary tumors. Oncogene 13:2033-2038, 1996.
122. Donehower LA, Harvey M, Slagle BL, et al. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356:215-221, 1992.
123. Lowe SW, Schmitt EM, Smith SW, Osborne BA, Jacks T. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362:847-849, 1993.
124. Harvey M, McArthur MJ, Montgomery CA Jr, Bradley A, Donehower LA. Genetic background alters the spectrum of tumors that develop in p53-deficient mice. FASEB J 7:938-943, 1993.
125. Jacks T, Remington L, Williams BO, et al. Tumor spectrum analysis in p53-mutant mice. Curr Biol 4:1-7, 1994.
126. Purdie CA, Harrison DJ, Peter A, et al. Tumour incidence, spectrum and ploidy in mice with a large deletion in the p53 gene. Oncogene 9:603-609, 1994.
127. Serrano M, Lee HW, Chin L, Cordon-Cardo C, Beach D, DePinho RA. Role of the INK4a locus in tumor suppression and cell mortality. Cell 85:27-37, 1996.
128. Brugarolas J, Chandrasekaran C, Gordon JI, Beach D, Jacks T, Hannon GJ. Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature 377:552-557, 1995.
129. CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control. Cell 82:675-684, 1995.
130. Kip1-deficient mice. Cell 85:733-744, 1996.
131. Kip1. Cell 85:721-732, 1996.
132. Kip1, A cyclin-Cdk inhibitor, links transforming growth factor-β and contact inhibition to cell cycle arrest. Genes Dev 8:9-22, 1994.
133. Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitoqenic signals. Cell 78:59-66, 1994.
134. Bianchi AB, Fischer SM, Robles AI, Rinchik EM, Conti CJ. Overexpression of cyclin D1 in mouse skin carcinogenesis. Oncogene 8:1127-1133, 1993.
135. Wang TC, Cardiff RD, Zukerberg L, Lees E, Arnold A, Schmidt EV. Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature 369:669-671, 1994.
136. Mitsunaga SI, Zhang SY, Ruggeri BA, et al. Positive immunohistochemical staining of p53 and cyclin D in advanced mouse skin tumors, but not in precancerous lesions produced by benzo[a]pyrene. Carcinogenesis 16:1629-1636, 1995.
137. Robles AI, Larcher F, Whalin RB, et al. Expression of cyclin D1 in epithelial tissues of transgenic mice results in epidermal hyperproliferation severe thymic hyperplasia. Proc Natl Acad Sci USA 93:7634-7638, 1996.
138. Bortner DM, Rosenberg MP. Induction of mammary gland hyperplasia and carcinomas in transgenic mice expressing human cyclin E. Mol Cell Biol 17:453-459, 1997.
139. Bartkova J, Lukas J, Müller H, Lützhoft D, Strauss M, Bartek J. Cyclin D1 protein expression and function in human breast cancer. Int J Cancer 57:353-361, 1994.
140. Bartkova J, Lukas J, Strauss M, Bartek J. The PRAD-1/cyclin D1 oncogene product accumulates aberrantly in a subset of colorectal carcinomas. Int J Cancer 58:568-573, 1994.
141. Callender T, El-Naggar AK, Lee MS, Frankenthaler R, Luna MA, Batsakis JG. PRAD-1 (CCND1)/cyclin D1 oncogene amplification in primary head and neck squamous cell carcinoma. Cancer 74:152-158, 1994.
142. Arnold A. The cyclin D1/PRAD1 oncogene in human neoplasia. J Invest Med 43:543-549, 1995.
143. Weinstat-Saslow D, Merino MJ, Manrow RE, et al. Overexpression of cyclin D mRNA distinguishes invasive and in situ breast carcinomas from non-malignant lesions. Nat Med 1:1257-1260, 1995.
144. Inohara S, Kitagawa K, Kitano Y. Expression of cyclin D1 and p53 protein in various malignant skin tumors. Dermatology 192:94-98, 1996.
145. Cheo DL, Meira LB, Hammer RE, Burns DK, Doughty ATB, Friedberg EC. Synergistic interactions between XPC and p53 mutations in double-mutant mice: Neural tube abnormalities and accelerated UV radiation-induced skin cancer. Curr Biol 6:1691-1694, 1996.
146. Sekiguchi M, Nakabeppu Y, Sakumi K, Tuzuki T. DNA repair methyltransferase as a molecular device for preventing mutation and cancer. J Cancer Res Clin Oncol 122: 199-206, 1996.
147. n mouse embryos. Dev Dyn 206:239-247, 1996.
148. Chaillet JR, Vogt TF, Beier DR, Leder P. Parental-specific methylation of an imprinted transgene is established during gametogenesis and progressively changes during embryogenesis. Cell 66:77-83, 1991.
149. Robbins RJ, Swam JL. C-myc protooncogene modulates cardiac hypertrophic growth in transgenic mice. Am J Physiol 262:590-597, 1992.
150. Dom sex reversal. Nat Genet 6:245-250, 1994.
151. Eicher EM. Sex and trinucleotide repeats. Nat Genet 6:221-223, 1994.
152. Ashley CT Jr, Warren ST. Trinucleotide repeat expansion and human disease. Annu Rev Genet 29:703-728, 1995.
153. Moser AR, Mattes EM, Dove WF, Lindstrom MJ, Haag JD, Gould MN, ApcMin, a mutation in the murine/Apc gene, predisposes to mammary carcinomas and focal alveolar hyperplasias. Proc Natl Acad Sci USA 90:8977-8981, 1993.
154. Fodde R, Edelmann W, Yang K, et al. A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors. Proc Natl Acad Sci USA 91:8969-8973, 1994.
155. Yamasaki L, Jacks T, Bronson R, Goillot E, Harlow E, Dyson NJ. Tumor induction and tissue atrophy in mice lacking E2F-1. Cell 85:537-548, 1996.
156. Kreidberg JA, Sariola H, Loring JM, et al. WT-1 is required for early kidney development. Cell 74:679-691, 1993.
157. Hilberg F, Aguzzi A, Howells N, Wagner EF. c-jun is essential for normal mouse development and hepatogenesis. Nature 365:179-181, 1993.
158. Johnson RS, Van Lingen B, Papaioannou VE, Spiegelman BM. A null mutation at the c-jun locus causes embryonic lethality and retarded cell growth in culture. Genes Dev 7:1309-1317, 1993.
159. Field SJ, Johnson RS, Mortensen RM, Papaioannou VE, Spiegelman BM, Greenberg ME. Growth and differentiation of embryonic stem cells that lack an intact c-fos gene. Proc Natl Acad Sci USA 89:9306-9310, 1992.
160. Johnson RS, Spiegelman BM, Papaioannou V. Pleiotropic effects of a null mutation in the c-fos proto-oncogene. Cell 71:577-586, 1992.
161. Wang Z-Q, Ovitt C, Grigonadis AE, Möhle-Steinlein U, Rüther U, Wagner EF. Bone and haematopoietic defects in mice lacking c-fos. Nature 360:741-745, 1992.
162. Grigoriadis AE, Wang Z-Q, Cecchini MG, et al. c-Fos: A key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science 266:443-448, 1994.
163. Gruda MC, Van Amsterdam J, Rizzo CA, Durham SK, Lira S, Bravo R. Expression of FosB during mouse development: Normal development of FosB knockout mice. Oncogene 12:2177-2185, 1996.
164. Baker S, Bronner C, Zhang L, et al. Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell 82:309-319, 1995.
165. Reitmair AH, Schmits R, Ewel A, et al. MSH2 deficient mice are viable and susceptible to lymphoid tumours. Nat Genet 11:64-70, 1995.
166. Reitmair AH, Redston M, Cai JC, et al. Spontaneous intestinal carcinomas and skin neoplasms in Msh2-deficient mice. Cancer Res 56:3842-3849, 1996.
167. Baker SM, Plug AW, Prolla TA, et al. Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nat Genet 13:336-342, 1996.
168. Nakane H, Takeuchi S, Yuba S, et al. High incidence of ultraviolet-B-or chemical-carcinogen-induced skin tumours in mice lacking the xeroderma pigmentosum group A gene. Nature 377: 165-168, 1995.
169. Miyauchi-Hashimoto H, Tanaka K, Horio T. Enhanced inflammation and immunosuppression by ultraviolet radiation in xeroderma pigmentosum group A (XPA) model mice. J Invest Dermatol 107:343-348, 1996.
170. Sands AT, Abuin A, Sanchez A, Conti CJ, Bradley A. High susceptibility to ultraviolet-induced carcinogenesis in mice lacking XPC. Nature 377:162-165, 1995.
171. Wang Z-Q, Auer B, Stingl L, et al. Mice lacking ADPRT and poly(ADP-nbosyl)ation develop normally but are susceptible to skin disease. Genes Dev 9:509-520, 1995.
172. Tsuzuki T, Sakumi K, Shiraishi A, et al. Targeted disruption of the DNA repair methyltransferase gene renders mice hypersensitive to alkylating agent. Carcinogenesis 17:1215-1220, 1996.
173. Elson A, Wang YQ, Daugherty CJ, et al. Pleiotropic defects in ataxia-telangiectasia protein-deficient mice. Proc Natl Acad Sci USA 93:13084-13089, 1996.
174. Xu Y, Ashley T, Brainerd EE, Bronson RT, Meyn MS, Baltimore D. Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma. Genes Dev 10:2411-2422, 1996.
175. McWhir J, Selfridge J, Harrison DJ, Squires S, Melton DW. Mice with DNA repair gene (ERCC-1) deficiency have elevated levels of p53, liver nuclear abnormalities and die before weaning. Nat Genet 5:217-224, 1993.
176. Tsuzuki T, Fujii Y, Sakumi K, et al. Targeted disruption of the Rad51 gene leads to lethality in embryonic mice. Proc Natl Acad Sci USA 93:6236-6240, 1996.
177. Clarke AR, Maandag ER, Van Roon M, et al. Requirement for a functional Rb-1 gene in murine development. Nature 359:328-330, 1992.
178. Jacks T, Fazeli A, Schmitt EM, Bronson RT, Goodell MA, Weinberg RA. Effects of an Rb mutation in the mouse. Nature 359:295-300, 1992.
179. Sicinski P, Donaher JL, Parker SB, et al. Cyclin D1 provides a link between development and oncogenesis in the retina and breast. Cell 82:621-630, 1995.